Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity

Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (Selenof) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof’s potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing.

Download Full-text

The Therapeutic Efficacy of Curcumin vs. Metformin in Modulating the Gut Microbiota in NAFLD Rats: A Comparative Study

Frontiers in Microbiology ◽

10.3389/fmicb.2020.555293 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ruifang Li ◽

Yurong Yao ◽

Pengfei Gao ◽

Shurui Bu

Keyword(s):

Gut Microbiota ◽

Therapeutic Efficacy ◽

Structural Changes ◽

Intestinal Barrier ◽

Inflammatory Factors ◽

Beneficial Bacteria ◽

Alcoholic Fatty Liver ◽

Barrier Integrity ◽

Before And After ◽

Intestinal Barrier Integrity

Structural disruption of gut microbiota is closely related to the occurrence of non-alcoholic fatty liver disease (NAFLD). Previous research has demonstrated that both curcumin (CUR) and metformin (MET) have a therapeutic effect against NAFLD and play a role in modulating the gut microbiota. However, there is a lack of direct comparison between the two medications in terms of the therapeutic efficacy and the regulatory effect on gut microbiota. In this study, we administered either CUR or MET to rats with high-fat diet (HFD)-induced obesity to observe changes in body parameters, biochemical parameters, liver, and ileum pathology and gut microbiota, and used next generation sequencing and multivariate analysis to evaluate the structural changes of gut microbiota in a NAFLD rat model before and after CUR and MET intervention. It was found that both CUR and MET attenuated hepatic ectopic fat deposition, alleviated inflammatory factors, and improved intestinal barrier integrity in HFD-fed rats. More importantly, CUR and MET reduced the Firmicutes/Bacteroidetes ratio and reverted the composition of the HFD-disrupted gut microbiota. Both CUR and MET treatments effectively modified the gut microbiome, enriched the abundance of beneficial bacteria and reduced opportunistic pathogens in obese rats. The abundance of Butyricicoccus was increased while the abundance of Dorea was decreased in HFD + CUR group. Besides, some beneficial bacteria such as Prevotella were increased in MET-treated animals. Spearman’s correlation analysis showed that Helicobacter, Akkermansia, Desulfovibrio, Romboutsia, Corynebacterium, Lactobacillus, Ruminococcaceae_unclassified, Lachnospiraceae_unclassified, and Clostridiales_unclassified showed significantly positive correlations with TG, TC, LDL-C, GLU, IL-6, IL-1β, and TNF-α, and negative correlations with HDL-C (both p < 0.05). However, Prevotella and Stomatobaculum showed an opposite trend. In summary, CUR and MET showed similar effects in alleviating hepatic steatosis, improving intestinal barrier integrity and modulating gut microbiota in HFD-induced obesity rats, and therefore may prove to be a novel adjunctive therapy for NAFLD.

Download Full-text

Chronic opioid use modulates human enteric microbiota and intestinal barrier integrity

Gut Microbes ◽

10.1080/19490976.2021.1946368 ◽

2021 ◽

Vol 13 (1) ◽

pp. 1946368

Author(s):

Angélica Cruz-Lebrón ◽

Ramona Johnson ◽

Claire Mazahery ◽

Zach Troyer ◽

Samira Joussef-Piña ◽

...

Keyword(s):

Intestinal Barrier ◽

Opioid Use ◽

Barrier Integrity ◽

Intestinal Barrier Integrity ◽

Chronic Opioid Use

Download Full-text

Pharmacokinetic Analysis of Carnosic Acid and Carnosol in Standardized Rosemary Extract and the Effect on the Disease Activity Index of DSS-Induced Colitis

Nutrients ◽

10.3390/nu13030773 ◽

2021 ◽

Vol 13 (3) ◽

pp. 773

Author(s):

Jacob P. Veenstra ◽

Bhaskar Vemu ◽

Restituto Tocmo ◽

Mirielle C. Nauman ◽

Jeremy J. Johnson

Keyword(s):

Disease Activity ◽

Activity Index ◽

Intestinal Barrier ◽

Disease Activity Index ◽

Carnosic Acid ◽

Rosemary Extract ◽

Oral Gavage ◽

Barrier Integrity ◽

Dietary Phytochemicals ◽

Intestinal Barrier Integrity

Rosemary extract (RE) is an approved food preservative in the European Union and contains dietary phytochemicals that are beneficial for gastrointestinal health. This study investigated the effects of RE on dextran sodium sulfate (DSS)-induced colitis and also determined the pharmacokinetics of dietary phytochemicals administered to mice via oral gavage. Individual components of rosemary extract were separated and identified by LC–MS/MS. The pharmacokinetics of two major diterpenes from RE, carnosic acid (CA) and carnosol (CL), administered to mice via oral gavage were determined. Then, the effect of RE pre-treatment on the disease activity index (DAI) of DSS-induced colitis in mice was investigated. The study determined that 100 mg/kg RE significantly improved DAI in DSS-induced colitis compared to negative control. Sestrin 2 protein expression, which increased with DSS exposure, was reduced with RE treatment. Intestinal barrier integrity was also shown to improve via fluorescein isothiocyanate (FITC)–dextran administration and Western blot of zonula occludens-1 (ZO-1), a tight junction protein. Rosemary extract was able to improve the DAI of DSS-induced colitis in mice at a daily dose of 100 mg/kg and showed improvement in the intestinal barrier integrity. This study suggests that RE can be an effective preventative agent against IBD.

Download Full-text

Intestinal barrier integrity and inflammatory bowel disease: Stem cell‐based approaches to regenerate the barrier

Journal of Tissue Engineering and Regenerative Medicine ◽

10.1002/term.2506 ◽

2017 ◽

Vol 12 (4) ◽

pp. 923-935 ◽

Cited By ~ 19

Author(s):

Fredrik E.O. Holmberg ◽

Jannie Pedersen ◽

Peter Jørgensen ◽

Christoffer Soendergaard ◽

Kim B. Jensen ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Stem Cell ◽

Bowel Disease ◽

Intestinal Barrier ◽

Barrier Integrity ◽

Inflammatory Bowel ◽

Intestinal Barrier Integrity

Download Full-text

BDNF modulates intestinal barrier integrity through regulating the expression of tight junction proteins

Neurogastroenterology & Motility ◽

10.1111/nmo.12967 ◽

2016 ◽

Vol 29 (3) ◽

pp. e12967 ◽

Cited By ~ 10

Author(s):

Y.-B. Yu ◽

D.-Y. Zhao ◽

Q.-Q. Qi ◽

X. Long ◽

X. Li ◽

...

Keyword(s):

Tight Junction ◽

Intestinal Barrier ◽

Tight Junction Proteins ◽

Barrier Integrity ◽

Intestinal Barrier Integrity ◽

Junction Proteins

Download Full-text

HO-1/CO Maintains Intestinal Barrier Integrity through NF-κB/MLCK Pathway in Intestinal HO-1-/- Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6620873 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Zhenling Zhang ◽

Lijing Zhang ◽

Qiuping Zhang ◽

Bojia Liu ◽

Fang Li ◽

...

Keyword(s):

Molecular Mechanisms ◽

Intestinal Barrier ◽

Heme Oxygenase 1 ◽

Zinc Protoporphyrin ◽

Barrier Integrity ◽

Tnf Α ◽

Intestinal Barrier Integrity ◽

Deficient Mice

Background. Intestinal barrier injury is an important contributor to many diseases. We previously found that heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal barrier. This study is aimed at elucidating the molecular mechanisms of HO-1/CO in barrier loss. Materials and Methods. We induced gut leakiness by injecting carbon tetrachloride (CCl4) to wildtype or intestinal HO-1-deficient mice. In addition, we administrated tumor necrosis factor-α (TNF-α) to cells with gain- or loss-of-HO-1 function. The effects of HO-1/CO maintaining intestinal barrier integrity were investigated in vivo and in vitro. Results. Cobalt protoporphyrin and CO-releasing molecule-2 alleviated colonic mucosal injury and TNF-α levels; upregulated tight junction (TJ) expression; and inhibited epithelial IκB-α degradation and phosphorylation, NF-κB p65 phosphorylation, long MLCK expression, and MLC-2 phosphorylation after administration of CCl4. Zinc protoporphyrin completely reversed these effects. These findings were further confirmed in vitro, using Caco-2 cells with gain- or loss-of-HO-1-function after TNF-α. Pretreated with JSH-23 (NF-κB inhibitor) or ML-7 (long MLCK inhibitor), HO-1 overexpression prevented TNF-α-induced TJ disruption, while HO-1 shRNA promoted TJ damage even in the presence of JSH-23 or ML-7, thus suggesting that HO-1 dependently protected intestinal barrier via the NF-κB p65/MLCK/p-MLC-2 pathway. Intestinal HO-1-deficient mice further demonstrated the effects of HO-1 in maintaining intestinal barrier integrity and its relative mechanisms. Alleviated hepatic fibrogenesis and serum ALT levels finally confirmed the clinical significance of HO-1/CO repairing barrier loss in liver injury. Conclusion. HO-1/CO maintains intestinal barrier integrity through the NF-κB/MLCK pathway. Therefore, the intestinal HO-1/CO-NF-κB/MLCK system is a potential therapeutic target for diseases with a leaky gut.

Download Full-text